Skip to main content
SpringerLink
Log in

Cellular Dynamics Controlled by Phosphatases

  • Review Article
  • Published:
Journal of the Indian Institute of Science Aims and scope

Abstract

Protein phosphorylation, a fundamental post-translation modification that acts as a backbone of signaling networks, is essential for multiple aspects of eukaryote physiology. Phosphorylation status of a substrate is dependent on opposing activities of two distinct enzymes, where the relevant kinase catalyzes the modification and is reversed by a phosphatase. Historically, kinases have been at the research forefront; however, phosphatases have gained importance with many studies revealing predominant roles for these enzymes in controlling the cellular responses. Phosphatases are known to attenuate or amplify signaling by operating both as early, as well as delayed regulators of signal transduction. This review is focused on describing the versatile roles of phosphatases in controlling different cellular pathways through their spatio-temporal dynamics during signaling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1:
Figure 2:
Figure 3:
Figure 4:
Figure 5:
Figure 6:
Figure 7:

Similar content being viewed by others

References

  1. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298:1912–1934

    Article  Google Scholar 

  2. Manning G, Plowman GD, Hunter T, Sudarsanam S (2002) Evolution of protein kinase signaling from yeast to man. Trends Biochem Sci 27:514–520

    Article  Google Scholar 

  3. Cohen P (2002) The origins of protein phosphorylation. Nat Cell Biol 4:E127–E130

    Article  Google Scholar 

  4. Cohen P (1994) The discovery of protein phosphatases: from chaos and confusion to an understanding of their role in cell regulation and human disease. BioEssays 16:583–588

    Article  Google Scholar 

  5. Heinrich R, Neel BG, Rapoport TA (2002) Mathematical models of protein kinase signal transduction. Mol Cell 9:957–970

    Article  Google Scholar 

  6. Hornberg JJ, Bruggeman FJ, Binder B, Geest CR, de Vaate AJ, Lankelma J et al (2005) Principles behind the multifarious control of signal transduction. ERK phosphorylation and kinase/phosphatase control. FEBS J 272:244–258

    Article  Google Scholar 

  7. Das AK, Helps NR, Cohen PT, Barford D (1996) Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution. Embo J 15:6798–6809

    Google Scholar 

  8. Schweighofer A, Hirt H, Meskiene I (2004) Plant PP2C phosphatases: emerging functions in stress signaling. Trends Plant Sci 9:236–243

    Article  Google Scholar 

  9. Cho US, Xu W (2007) Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme. Nature 445:53–57

    Article  Google Scholar 

  10. Xu Y, Xing Y, Chen Y, Chao Y, Lin Z, Fan E et al (2006) Structure of the protein phosphatase 2A holoenzyme. Cell 127:1239–1251

    Article  Google Scholar 

  11. Archambault J, Pan G, Dahmus GK, Cartier M, Marshall N, Zhang S et al (1998) FCP1, the RAP74-interacting subunit of a human protein phosphatase that dephosphorylates the carboxyl-terminal domain of RNA polymerase IIO. J Biol Chem 273:27593–27601

    Article  Google Scholar 

  12. Meinhart A, Kamenski T, Hoeppner S, Baumli S, Cramer P (2005) A structural perspective of CTD function. Genes Dev 19:1401–1415

    Article  Google Scholar 

  13. Buist A, Zhang YL, Keng YF, Wu L, Zhang ZY, den Hertog J (1999) Restoration of potent protein-tyrosine phosphatase activity into the membrane-distal domain of receptor protein-tyrosine phosphatase alpha. Biochemistry 38:914–922

    Article  Google Scholar 

  14. Blanchetot C, Tertoolen LG, Overvoorde J, den Hertog J (2002) Intra- and intermolecular interactions between intracellular domains of receptor protein-tyrosine phosphatases. J Biol Chem 277:47263–47269

    Article  Google Scholar 

  15. Jiang G, den Hertog J, Hunter T (2000) Receptor-like protein tyrosine phosphatase alpha homodimerizes on the cell surface. Mol Cell Biol 20:5917–5929

    Article  Google Scholar 

  16. Garton AJ, Burnham MR, Bouton AH, Tonks NK (1997) Association of PTP-PEST with the SH3 domain of p130cas; a novel mechanism of protein tyrosine phosphatase substrate recognition. Oncogene 15:877–885

    Article  Google Scholar 

  17. Pulido R, Zuniga A, Ullrich A (1998) PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ERK2 by association through a kinase interaction motif. EMBO J 17:7337–7350

    Article  Google Scholar 

  18. Mustelin T (2007) A brief introduction to the protein phosphatase families. Methods Mol Biol 365:9–22

    Google Scholar 

  19. Begley MJ, Dixon JE (2005) The structure and regulation of myotubularin phosphatases. Curr Opin Struct Biol 15:614–620

    Article  Google Scholar 

  20. Laporte J, Bedez F, Bolino A, Mandel JL (2003) Myotubularins, a large disease-associated family of cooperating catalytically active and inactive phosphoinositides phosphatases. Hum Mol Genet 12(2):R285–R292

    Article  Google Scholar 

  21. Li X, Oghi KA, Zhang J, Krones A, Bush KT, Glass CK et al (2003) Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature 426:247–254

    Article  Google Scholar 

  22. Tootle TL, Silver SJ, Davies EL, Newman V, Latek RR, Mills IA et al (2003) The transcription factor Eyes absent is a protein tyrosine phosphatase. Nature 426:299–302

    Article  Google Scholar 

  23. Sun XJ, Rothenberg P, Kahn CR, Backer JM, Araki E, Wilden PA et al (1991) Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 352:73–77

    Article  Google Scholar 

  24. Saltiel AR, Pessin JE (2002) Insulin signaling pathways in time and space. Trends Cell Biol 12:65–71

    Article  Google Scholar 

  25. Shi Y, Wang J, Chandarlapaty S, Cross J, Thompson C, Rosen N et al (2014) PTEN is a protein tyrosine phosphatase for IRS1. Nat Struct Mol Biol 21:522–527

    Article  Google Scholar 

  26. Ahmad F, Considine RV, Goldstein BJ (1995) Increased abundance of the receptor-type protein-tyrosine phosphatase LAR accounts for the elevated insulin receptor dephosphorylating activity in adipose tissue of obese human subjects. J Clin Invest 95:2806–2812

    Article  Google Scholar 

  27. Ahmad F, Goldstein BJ (1997) Functional association between the insulin receptor and the transmembrane protein-tyrosine phosphatase LAR in intact cells. J Biol Chem 272:448–457

    Article  Google Scholar 

  28. Zhang WR, Li PM, Oswald MA, Goldstein BJ (1996) Modulation of insulin signal transduction by eutopic overexpression of the receptor-type protein-tyrosine phosphatase LAR. Mol Endocrinol 10:575–584

    Google Scholar 

  29. Kulas DT, Zhang WR, Goldstein BJ, Furlanetto RW, Mooney RA (1995) Insulin receptor signaling is augmented by antisense inhibition of the protein tyrosine phosphatase LAR. J Biol Chem 270:2435–2438

    Article  Google Scholar 

  30. Zabolotny JM, Kim YB, Peroni OD, Kim JK, Pani MA, Boss O et al (2001) Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance. Proc Natl Acad Sci USA 98:5187–5192

    Article  Google Scholar 

  31. Lammers R, Moller NP, Ullrich A (1997) The transmembrane protein tyrosine phosphatase alpha dephosphorylates the insulin receptor in intact cells. FEBS Lett 404:37–40

    Article  Google Scholar 

  32. Andersen JN, Elson A, Lammers R, Romer J, Clausen JT, Moller KB et al (2001) Comparative study of protein tyrosine phosphatase-epsilon isoforms: membrane localization confers specificity in cellular signalling. Biochem J 354:581–590

    Google Scholar 

  33. Kruger J, Brachs S, Trappiel M, Kintscher U, Meyborg H, Wellnhofer E et al (2015) Enhanced insulin signaling in density-enhanced phosphatase-1 (DEP-1) knockout mice. Mol Metab 4:325–336

    Article  Google Scholar 

  34. Rocchi S, Tartare-Deckert S, Sawka-Verhelle D, Gamha A, van Obberghen E (1996) Interaction of SH2-containing protein tyrosine phosphatase 2 with the insulin receptor and the insulin-like growth factor-I receptor: studies of the domains involved using the yeast two-hybrid system. Endocrinology 137:4944–4952

    Google Scholar 

  35. Kharitonenkov A, Schnekenburger J, Chen Z, Knyazev P, Ali S, Zwick E et al (1995) Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction. J Biol Chem 270:29189–29193

    Article  Google Scholar 

  36. Maegawa H, Hasegawa M, Sugai S, Obata T, Ugi S, Morino K et al (1999) Expression of a dominant negative SHP-2 in transgenic mice induces insulin resistance. J Biol Chem 274:30236–30243

    Article  Google Scholar 

  37. Arrandale JM, Gore-Willse A, Rocks S, Ren JM, Zhu J, Davis A et al (1996) Insulin signaling in mice expressing reduced levels of Syp. J Biol Chem 271:21353–21358

    Article  Google Scholar 

  38. Cheng A, Uetani N, Simoncic PD, Chaubey VP, Lee-Loy A, McGlade CJ et al (2002) Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Dev Cell 2:497–503

    Article  Google Scholar 

  39. Asante-Appiah E, Kennedy BP (2003) Protein tyrosine phosphatases: the quest for negative regulators of insulin action. Am J Physiol Endocrinol Metab 284:E663–E670

    Article  Google Scholar 

  40. Bandyopadhyay D, Kusari A, Kenner KA, Liu F, Chernoff J, Gustafson TA et al (1997) Protein-tyrosine phosphatase 1B complexes with the insulin receptor in vivo and is tyrosine-phosphorylated in the presence of insulin. J Biol Chem 272:1639–1645

    Article  Google Scholar 

  41. Dadke S, Kusari J, Chernoff J (2000) Down-regulation of insulin signaling by protein-tyrosine phosphatase 1B is mediated by an N-terminal binding region. J Biol Chem 275:23642–23647

    Article  Google Scholar 

  42. Salmeen A, Andersen JN, Myers MP, Tonks NK, Barford D (2000) Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B. Mol Cell 6:1401–1412

    Article  Google Scholar 

  43. Klaman LD, Boss O, Peroni OD, Kim JK, Martino JL, Zabolotny JM et al (2000) Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol Cell Biol 20:5479–5489

    Article  Google Scholar 

  44. Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL et al (1999) Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283:1544–1548

    Article  Google Scholar 

  45. Morrison DK (2012) MAP kinase pathways. Cold Spring Harb Perspect Biol 4(11):a011254. doi:10.1101/cshperspect.a011254

  46. Caunt CJ, Keyse SM (2013) Dual-specificity MAP kinase phosphatases (MKPs): shaping the outcome of MAP kinase signalling. FEBS J 280:489–504

    Article  Google Scholar 

  47. Massague J, Seoane J, Wotton D (2005) Smad transcription factors. Genes Dev 19:2783–2810

    Article  Google Scholar 

  48. Lin X, Duan X, Liang YY, Su Y, Wrighton KH, Long J et al (2006) PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell 125:915–928

    Article  Google Scholar 

  49. Bennett D, Alphey L (2002) PP1 binds Sara and negatively regulates Dpp signaling in Drosophila melanogaster. Nat Genet 31:419–423

    Google Scholar 

  50. Sapkota G, Knockaert M, Alarcon C, Montalvo E, Brivanlou AH, Massague J (2006) Dephosphorylation of the linker regions of Smad1 and Smad2/3 by small C-terminal domain phosphatases has distinct outcomes for bone morphogenetic protein and transforming growth factor-beta pathways. J Biol Chem 281:40412–40419

    Article  Google Scholar 

  51. Wrighton KH, Willis D, Long J, Liu F, Lin X, Feng XH (2006) Small C-terminal domain phosphatases dephosphorylate the regulatory linker regions of Smad2 and Smad3 to enhance transforming growth factor-beta signaling. J Biol Chem 281:38365–38375

    Article  Google Scholar 

  52. Chen HB, Shen J, Ip YT, Xu L (2006) Identification of phosphatases for Smad in the BMP/DPP pathway. Genes Dev 20:648–653

    Article  Google Scholar 

  53. Knockaert M, Sapkota G, Alarcon C, Massague J, Brivanlou AH (2006) Unique players in the BMP pathway: small C-terminal domain phosphatases dephosphorylate Smad1 to attenuate BMP signaling. Proc Natl Acad Sci USA 103:11940–11945

    Article  Google Scholar 

  54. Mueller PR, Coleman TR, Dunphy WG (1995) Cell cycle regulation of a Xenopus Wee1-like kinase. Mol Biol Cell 6:119–134

    Article  Google Scholar 

  55. Dunphy WG, Kumagai A (1991) The cdc25 protein contains an intrinsic phosphatase activity. Cell 67:189–196

    Article  Google Scholar 

  56. Kumagai A, Dunphy WG (1991) The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system. Cell 64:903–914

    Article  Google Scholar 

  57. Blomberg I, Hoffmann I (1999) Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to premature activation of cyclin E- and cyclin A-dependent kinases. Mol Cell Biol 19:6183–6194

    Article  Google Scholar 

  58. Hoffmann I, Draetta G, Karsenti E (1994) Activation of the phosphatase activity of human cdc25A by a cdk2-cyclin E dependent phosphorylation at the G1/S transition. EMBO J 13:4302–4310

    Google Scholar 

  59. Jinno S, Suto K, Nagata A, Igarashi M, Kanaoka Y, Nojima H et al (1994) Cdc25A is a novel phosphatase functioning early in the cell cycle. EMBO J 13:1549–1556

    Google Scholar 

  60. Lindqvist A, Kallstrom H, Lundgren A, Barsoum E, Rosenthal CK (2005) Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating cyclin B1-Cdk1 at the centrosome. J Cell Biol 171:35–45

    Article  Google Scholar 

  61. Mailand N, Podtelejnikov AV, Groth A, Mann M, Bartek J, Lukas J (2002) Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability. EMBO J 21:5911–5920

    Article  Google Scholar 

  62. Boutros R, Dozier C, Ducommun B (2006) The when and wheres of CDC25 phosphatases. Curr Opin Cell Biol 18:185–191

    Article  Google Scholar 

  63. Gabrielli BG, De Souza CP, Tonks ID, Clark JM, Hayward NK, Ellem KA (1996) Cytoplasmic accumulation of cdc25B phosphatase in mitosis triggers centrosomal microtubule nucleation in HeLa cells. J Cell Sci 109(Pt 5):1081–1093

    Google Scholar 

  64. De Souza CP, Ellem KA, Gabrielli BG (2000) Centrosomal and cytoplasmic Cdc2/cyclin B1 activation precedes nuclear mitotic events. Exp Cell Res 257:11–21

    Article  Google Scholar 

  65. Gabrielli BG, Clark JM, McCormack AK, Ellem KA (1997) Hyperphosphorylation of the N-terminal domain of Cdc25 regulates activity toward cyclin B1/Cdc2 but not cyclin A/Cdk2. J Biol Chem 272:28607–28614

    Article  Google Scholar 

  66. Turowski P, Franckhauser C, Morris MC, Vaglio P, Fernandez A, Lamb NJ (2003) Functional cdc25C dual-specificity phosphatase is required for S-phase entry in human cells. Mol Biol Cell 14:2984–2998

    Article  Google Scholar 

  67. Garner-Hamrick PA, Fisher C (1998) Antisense phosphorothioate oligonucleotides specifically down-regulate cdc25B causing S-phase delay and persistent antiproliferative effects. Int J Cancer 76:720–728

    Article  Google Scholar 

  68. Vandre DD, Wills VL (1992) Inhibition of mitosis by okadaic acid: possible involvement of a protein phosphatase 2A in the transition from metaphase to anaphase. J Cell Sci 101(Pt 1):79–91

    Google Scholar 

  69. Skoufias DA, Indorato RL, Lacroix F, Panopoulos A, Margolis RL (2007) Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed. J Cell Biol 179:671–685

    Article  Google Scholar 

  70. Burgess A, Vigneron S, Brioudes E, Labbe JC, Lorca T, Castro A (2010) Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance. Proc Natl Acad Sci USA 107:12564–12569

    Article  Google Scholar 

  71. Castilho PV, Williams BC, Mochida S, Zhao Y, Goldberg ML (2009) The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK phosphosites. Mol Biol Cell 20:4777–4789

    Article  Google Scholar 

  72. Vigneron S, Brioudes E, Burgess A, Labbe JC, Lorca T, Castro A (2009) Greatwall maintains mitosis through regulation of PP2A. EMBO J 28:2786–2793

    Article  Google Scholar 

  73. Zhao Y, Haccard O, Wang R, Yu J, Kuang J, Jessus C et al (2008) Roles of Greatwall kinase in the regulation of cdc25 phosphatase. Mol Biol Cell 19:1317–1327

    Article  Google Scholar 

  74. Lorca T, Bernis C, Vigneron S, Burgess A, Brioudes E, Labbe JC et al (2009) Constant regulation of both the MPF amplification loop and the Greatwall-PP2A pathway is required for metaphase II arrest and correct entry into the first embryonic cell cycle. J Cell Sci 123:2281–2291

    Article  Google Scholar 

  75. Gharbi-Ayachi A, Labbe JC, Burgess A, Vigneron S, Strub JM, Brioudes E et al (2010) The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A. Science 330:1673–1677

    Article  Google Scholar 

  76. Mochida S, Maslen SL, Skehel M, Hunt T (2010) Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis. Science 330:1670–1673

    Article  Google Scholar 

  77. Nasmyth K, Haering CH (2009) Cohesin: its roles and mechanisms. Annu Rev Genet 43:525–558

    Article  Google Scholar 

  78. Hauf S, Roitinger E, Koch B, Dittrich CM, Mechtler K, Peters JM (2005) Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2. PLoS Biol 3:e69

    Article  Google Scholar 

  79. Kitajima TS, Kawashima SA, Watanabe Y (2004) The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis. Nature 427:510–517

    Article  Google Scholar 

  80. Llano E, Gomez R, Gutierrez-Caballero C, Herran Y, Sanchez-Martin M, Vazquez-Quinones L et al (2008) Shugoshin-2 is essential for the completion of meiosis but not for mitotic cell division in mice. Genes Dev 22:2400–2413

    Article  Google Scholar 

  81. McGuinness BE, Hirota T, Kudo NR, Peters JM, Nasmyth K (2005) Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells. PLoS Biol 3:e86

    Article  Google Scholar 

  82. Salic A, Waters JC, Mitchison TJ (2004) Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis. Cell 118:567–578

    Article  Google Scholar 

  83. Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA et al (2006) Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature 441:46–52

    Article  Google Scholar 

  84. Riedel CG, Katis VL, Katou Y, Mori S, Itoh T, Helmhart W et al (2006) Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 441:53–61

    Article  Google Scholar 

  85. Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H (2006) PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell 10:575–585

    Article  Google Scholar 

  86. Wittmann T, Hyman A, Desai A (2001) The spindle: a dynamic assembly of microtubules and motors. Nat Cell Biol 3:E28–E34

    Article  Google Scholar 

  87. Helps NR, Luo X, Barker HM, Cohen PT (2000) NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1. Biochem J 349:509–518

    Article  Google Scholar 

  88. Meraldi P, Nigg EA (2001) Centrosome cohesion is regulated by a balance of kinase and phosphatase activities. J Cell Sci 114:3749–3757

    Google Scholar 

  89. Mi J, Guo C, Brautigan DL, Larner JM (2007) Protein phosphatase-1alpha regulates centrosome splitting through Nek2. Cancer Res 67:1082–1089

    Article  Google Scholar 

  90. Sumara I, Gimenez-Abian JF, Gerlich D, Hirota T, Kraft C, de la Torre C et al (2004) Roles of polo-like kinase 1 in the assembly of functional mitotic spindles. Curr Biol 14:1712–1722

    Article  Google Scholar 

  91. Girdler F, Gascoigne KE, Eyers PA, Hartmuth S, Crafter C, Foote KM et al (2006) Validating Aurora B as an anti-cancer drug target. J Cell Sci 119:3664–3675

    Article  Google Scholar 

  92. Bayliss R, Sardon T, Vernos I, Conti E (2003) Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Mol Cell 12:851–862

    Article  Google Scholar 

  93. Sessa F, Mapelli M, Ciferri C, Tarricone C, Areces LB, Schneider TR et al (2005) Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol Cell 18:379–391

    Article  Google Scholar 

  94. Huse M, Kuriyan J (2002) The conformational plasticity of protein kinases. Cell 109:275–282

    Article  Google Scholar 

  95. Zeng K, Bastos RN, Barr FA, Gruneberg U (2010) Protein phosphatase 6 regulates mitotic spindle formation by controlling the T-loop phosphorylation state of Aurora A bound to its activator TPX2. J Cell Biol 191:1315–1332

    Article  Google Scholar 

  96. Ruchaud S, Carmena M, Earnshaw WC (2007) Chromosomal passengers: conducting cell division. Nat Rev Mol Cell Biol 8:798–812

    Article  Google Scholar 

  97. Posch M, Khoudoli GA, Swift S, King EM, Deluca JG, Swedlow JR (2010) Sds22 regulates aurora B activity and microtubule-kinetochore interactions at mitosis. J Cell Biol 191:61–74

    Article  Google Scholar 

  98. Sugiyama K, Sugiura K, Hara T, Sugimoto K, Shima H, Honda K et al (2002) Aurora-B associated protein phosphatases as negative regulators of kinase activation. Oncogene 21:3103–3111

    Article  Google Scholar 

  99. Liu D, Vleugel M, Backer CB, Hori T, Fukagawa T, Cheeseman IM et al (2010) Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase. J Cell Biol 188:809–820

    Article  Google Scholar 

  100. Wan X, O’Quinn RP, Pierce HL, Joglekar AP, Gall WE, DeLuca JG et al (2009) Protein architecture of the human kinetochore microtubule attachment site. Cell 137:672–684

    Article  Google Scholar 

  101. Welburn JP, Vleugel M, Liu D, Yates JR 3rd, Lampson MA, Fukagawa T et al (2010) Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore-microtubule interface. Mol Cell 38:383–392

    Article  Google Scholar 

  102. Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8:379–393

    Article  Google Scholar 

  103. Stegmeier F, Amon A (2004) Closing mitosis: the functions of the Cdc14 phosphatase and its regulation. Annu Rev Genet 38:203–232

    Article  Google Scholar 

  104. Mocciaro A, Schiebel E (2010) Cdc14: a highly conserved family of phosphatases with non-conserved functions? J Cell Sci 123:2867–2876

    Article  Google Scholar 

  105. Mocciaro A, Berdougo E, Zeng K, Black E, Vagnarelli P, Earnshaw W et al (2010) Vertebrate cells genetically deficient for Cdc14A or Cdc14B retain DNA damage checkpoint proficiency but are impaired in DNA repair. J Cell Biol 189:631–639

    Article  Google Scholar 

  106. Ferrigno P, Langan TA, Cohen P (1993) Protein phosphatase 2A1 is the major enzyme in vertebrate cell extracts that dephosphorylates several physiological substrates for cyclin-dependent protein kinases. Mol Biol Cell 4:669–677

    Article  Google Scholar 

  107. Mayer-Jaekel RE, Ohkura H, Ferrigno P, Andjelkovic N, Shiomi K, Uemura T et al (1994) Drosophila mutants in the 55 kDa regulatory subunit of protein phosphatase 2A show strongly reduced ability to dephosphorylate substrates of p34cdc2. J Cell Sci 107(Pt 9):2609–2616

    Google Scholar 

  108. Mayer-Jaekel RE, Ohkura H, Gomes R, Sunkel CE, Baumgartner S, Hemmings BA et al (1993) The 55 kd regulatory subunit of Drosophila protein phosphatase 2A is required for anaphase. Cell 72:621–633

    Article  Google Scholar 

  109. Mochida S, Ikeo S, Gannon J, Hunt T (2009) Regulated activity of PP2A-B55 delta is crucial for controlling entry into and exit from mitosis in Xenopus egg extracts. EMBO J 28:2777–2785

    Article  Google Scholar 

  110. Schmitz MH, Held M, Janssens V, Hutchins JR, Hudecz O, Ivanova E et al (2010) Live-cell imaging RNAi screen identifies PP2A-B55alpha and importin-beta1 as key mitotic exit regulators in human cells. Nat Cell Biol 12:886–893

    Article  Google Scholar 

  111. Axton JM, Dombradi V, Cohen PT, Glover DM (1990) One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis. Cell 63:33–46

    Article  Google Scholar 

  112. Chen F, Archambault V, Kar A, Lio P, D’Avino PP, Sinka R et al (2007) Multiple protein phosphatases are required for mitosis in Drosophila. Curr Biol 17:293–303

    Article  Google Scholar 

  113. Wu JQ, Guo JY, Tang W, Yang CS, Freel CD, Chen C et al (2009) PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation. Nat Cell Biol 11:644–651

    Article  Google Scholar 

  114. Trinkle-Mulcahy L, Andersen J, Lam YW, Moorhead G, Mann M, Lamond AI (2006) Repo-Man recruits PP1 gamma to chromatin and is essential for cell viability. J Cell Biol 172:679–692

    Article  Google Scholar 

  115. Vagnarelli P, Hudson DF, Ribeiro SA, Trinkle-Mulcahy L, Spence JM, Lai F et al (2006) Condensin and Repo-Man-PP1 co-operate in the regulation of chromosome architecture during mitosis. Nat Cell Biol 8:1133–1142

    Article  Google Scholar 

  116. Qian J, Lesage B, Beullens M, Van Eynde A, Bollen M (2011) PP1/Repo-man dephosphorylates mitotic histone H3 at T3 and regulates chromosomal aurora B targeting. Curr Biol 21:766–773

    Article  Google Scholar 

  117. Kelly AE, Ghenoiu C, Xue JZ, Zierhut C, Kimura H, Funabiki H (2010) Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science 330:235–239

    Article  Google Scholar 

  118. Wang F, Dai J, Daum JR, Niedzialkowska E, Banerjee B, Stukenberg PT et al (2010) Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science 330:231–235

    Article  Google Scholar 

  119. Guttinger S, Laurell E, Kutay U (2009) Orchestrating nuclear envelope disassembly and reassembly during mitosis. Nat Rev Mol Cell Biol 10:178–191

    Article  Google Scholar 

  120. Thompson LJ, Bollen M, Fields AP (1997) Identification of protein phosphatase 1 as a mitotic lamin phosphatase. J Biol Chem 272:29693–29697

    Article  Google Scholar 

  121. Steen RL, Martins SB, Tasken K, Collas P (2000) Recruitment of protein phosphatase 1 to the nuclear envelope by A-kinase anchoring protein AKAP149 is a prerequisite for nuclear lamina assembly. J Cell Biol 150:1251–1262

    Article  Google Scholar 

  122. Landsverk HB, Kirkhus M, Bollen M, Kuntziger T, Collas P (2005) PNUTS enhances in vitro chromosome decondensation in a PP1-dependent manner. Biochem J 390:709–717

    Article  Google Scholar 

  123. Wei JH, Seemann J (2009) Mitotic division of the mammalian Golgi apparatus. Semin Cell Dev Biol 20:810–816

    Article  Google Scholar 

  124. Lowe M, Gonatas NK, Warren G (2000) The mitotic phosphorylation cycle of the cis-Golgi matrix protein GM130. J Cell Biol 149:341–356

    Article  Google Scholar 

  125. Brautigan DL (2013) Protein Ser/Thr phosphatases–the ugly ducklings of cell signalling. FEBS J 280:324–345

    Article  Google Scholar 

  126. Gingras AC, Caballero M, Zarske M, Sanchez A, Hazbun TR, Fields S et al (2005) A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity. Mol Cell Proteomics 4:1725–1740

    Article  Google Scholar 

  127. Glatter T, Wepf A, Aebersold R, Gstaiger M (2009) An integrated workflow for charting the human interaction proteome: insights into the PP2A system. Mol Syst Biol 5:237

    Article  Google Scholar 

  128. Shinde SR, Maddika S (2016) PTEN modulates EGFR late endocytic trafficking and degradation by dephosphorylating Rab7. Nat Commun 7:10689

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge the funding support provided by by Wellcome Trust/DBT India Alliance grant (to S.M; 500230/Z/11/Z). S.M. is a recipient of Department of Biotechnology’s Sr. IYBA award (BT/01/IYBA/2009). P.K. acknowledges the fellowship support from Council of Scientific and Industrial Research (CSIR), India.

Author information

Authors and Affiliations

  1. Laboratory of Cell Death and Cell Survival, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, 500001, India

    Parveen Kumar & Subbareddy Maddika

  2. Graduate Studies, Manipal University, Manipal, 576104, India

    Parveen Kumar

Authors
  1. Parveen Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Subbareddy Maddika
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Subbareddy Maddika.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, P., Maddika, S. Cellular Dynamics Controlled by Phosphatases. J Indian Inst Sci 97, 129–145 (2017). https://doi.org/10.1007/s41745-016-0016-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41745-016-0016-y

Keywords

Search

Navigation